Pediatric immunodeficiencies (PIDs) often result in life-threatening infections in children. Mutations in over 150 genes have been linked to these immunodeficiencies. However, the process of identifying mutations that result in PIDs is extremely labor intensive, and often not successful. We propose to develop a microRNA profile for children presenting with PIDs. MicroRNAs are a recently discovered class of small RNAs that regulate diverse biological processes including immune cell development and cancers. Importantly, microRNA profiling is emerging as a key diagnostic and prognostic indicator of tumorigenesis and autoimmunity. We hypothesize that children presenting with PIDs will express microRNA signature profiles distinct from normal controls. MicroRNA array signature profiles will be developed for diverse DiGeorge and hyper-IgM patients. The particular types of microRNAs detected in different PIDs will also be used as a prognostic indicator for complications such as cancers or infections. This will enable clinicians to introduce prophylactic therapies and recognize cancer potentials among diverse PIDs. PUBLIC HEALTH RELEVANCE: The cells of the innate and adaptive immune system coordinately function to eliminate bacterial and viral infections. Once they respond to an infection, the immune cells undergo a number of developmental changes, some of which are controlled by small RNA molecules called microRNAs. We propose to develop microRNA array profiles of patients presenting with pediatric immunodeficiencies. The information from such profiling will provide vastly improved diagnostic and prognostic measures for patients with various immunodeficiencies.